OBJECTIVE:: : Economic evaluation of early surgery compared to the endoscopy-first approach in chronic pancreatitis. SUMMARY BACKGROUND DATA:: In patients with painful chronic pancreatitis and a dilated main pancreatic duct, early surgery, as compared with an endoscopy-first approach, leads to more pain reduction with fewer interventions. However, it is unknown if early surgery is more cost-effective than the endoscopy-first approach. METHODS:: The multicenter Dutch ESCAPE trial randomized patients with chronic pancreatitis and a dilated main pancreatic duct between early surgery (surgery within 6 weeks) or the endoscopy-first approach in 30 centers (April 2011 - September 2016). Healthcare utilization was prospectively recorded up to 18 months after randomization. Unit costs of resources were determined, and cost-effectiveness and cost–utility analyses were performed from societal and healthcare perspectives. Primary outcomes were the costs per unit decrease on the Izbicki pain score and per gained quality-adjusted life-year. RESULTS:: In total, 88 patients were included in the analysis, with 44 patients randomized to each group. Total costs were lower in the early surgery group but did not reach statistical significance (mean difference &OV0556;????4,815 (95 per cent bias-corrected and accelerated confidence interval &OV0556;????13,113 to &OV0556;3,411; P=0.25). Early surgery had a probability percentage of 88.4% of being more cost-effective than the endoscopy-first approach at a willingness-to-pay threshold of &OV0556;0 per day per unit decrease on the Izbicki pain score. The probability percentage per additional gained QALY was 75.7% at a willingness-to-pay threshold of &OV0556;50,000. CONCLUSION:: In patients with painful chronic pancreatitis and a dilated main pancreatic duct, early surgery was more cost-effective than the endoscopy-first approach.